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  • 1
    ISSN: 1432-1440
    Keywords: Na-K-ATPase ; Ouabain ; Natriuretic hormone ; Intracellular electrolytes ; Peripheral vascular resistance ; Cardiac function ; Hypertension ; Calcium entry blockade ; Human studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An endogenous humoral factor which inhibits the sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase) enzyme in vitro has been incriminated recently of playing a pathogenetic role in experimental and human hypertension. The present study was therefore performed in six healthy volunteers to investigate the hemodynamic consequences of an inhibition of this enzyme by ouabain, a potent and specific inhibitor of Na-K-ATPase. In addition, the role of intracellular calcium as a potential mediator was studied indirectly by the administration of nifedipine, a potent calcium entry blocker with predominant vasodilator properties. Intravenous administration of 8.5 µg ouabain/kg body weight inhibited red blood cell (RBC) — Na-K-ATPase by 49% which was accompanied by a significant increase in RBC — ATP and a decrease in intracellular potassium concentrations. This enzyme inhibition resulted in a 24% increase in peripheral vascular resistance. The parallel decrease in cardiac output and heart rate, however, prevented a rise in arterial pressure. This increase in vascular resistance was completely abolished by pretreatment with nifedipine (10 mg orally). In the absence of an effect of nifedipine on Na-K-ATPase, its attenuation of the vasoconstrictor effect of ouabain suggests that the effects of ouabain on the vascular smooth muscle cell are mediated by intracellular calcium. These results demonstrate that inhibition of the Na-K-ATPase enzyme in vivo causes a marked peripheral vaso-constriction. They are also compatible with the concept that an endogenous inhibitor of Na-K-ATPase — in the presence of decreased baroreceptor reflex sensitivity due to blood volume expansion — may play a role in the pathogenesis of human arterial hypertension.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 60 (1982), S. 1234-1239 
    ISSN: 1432-1440
    Keywords: 8-arginine-vasopressin ; Hemodynamic effects ; inhibition of prostaglandin synthesis ; Renin ; Hypertension ; 8-Arginin-Vasopressin ; Hämodynamische Wirkungen ; Hemmung der Prostaglandin-Synthese ; Renin ; Hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bisher vorliegende Untersuchungen lassen vermuten, daß in einem normotensiven Organismus der vasopressorische Effekt von 8-Arginin-Vasopressin (AVP) effektiv durch cardiovaskuläre Reflexe abgeschwächt wird. Die Gabe von exogenem AVP führt zu nur vorübergehenden Pressorreaktionen trotz fortgeführter ADH-Infusion und deutlich erhöhter Plasma-AVP-Konzentrationen. Die vorliegende Untersuchung versucht den Mechanismus der nur vorübergehenden Blutdruckerhöhungen, die oft als “Tachyphylaxie” bezeichnet werden, weiter zu charakterisieren. Unsere Ergebnisse bei gesunden Versuchspersonen zeigen einen zweiphasigen Verlauf nach i.v. Gabe von AVP: eine initiale Phase, die durch cardiovaskuläre Reflexe gekennzeichnet ist und eine zweite Phase, während der sich der periphere Gefäßwiderstand normalisiert. Hemmung der Prostaglandin-Synthese mit Indomethacin schwächt die vaskuläre Gegenregulation auf exogenes AVP ab und läßt so eine prostaglandinvermittelte Vasodilatation als Reaktion auf AVP als Ursache der „Vasopressintachyphylaxie“ vermuten. Die Bedeutung des Renin-Angiotensin-Systems und unterschiedlicher regionaler hämodynamischer Effekte von AVP werden diskutiert.
    Notes: Summary Previous investigations suggest that in a normotensive organism the vasopressor effect of 8-arginine-vasopressin (AVP) is very effectively buffered by cardiovascular reflex mechanisms. Exogenous AVP administration shows only small, transient increases in blood pressure in spite of continued AVP-infusion and high plasma AVP concentrations. The present study aims to clarify the mechanism of the observed transient blood pressure elevations which are often referred to as “tachyphylaxis”. Our results in healthy subjects show a two phase response to exogenous AVP: an initial phase which is characterized by cardiac reflex mechanisms and a second phase during which a normalisation of the elevated total peripheral resistance occurs. Inhibition of prostaglandin synthesis with indomethacin almost completely attenuates this vascular counterregulation to exogenous AVP, thus providing evidence that a prostaglandin mediated vasodilation in response to AVP may be the underlying mechanism for “vasopressin tachyphylaxis”. The role of the renin-angiotensin-system and the importance of different regional hemodynamic effects of AVP are discussed.
    Type of Medium: Electronic Resource
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